The present invention relates to pure polyether urethanes and polyester urethanes based on aliphatic and/or cycloaliphatic diisocyanates. This invention also relates to the use of such pure polyurethane synthetic materials for biomedical applications. Thermoplastic polyurethane elastomers (TPU) have long been known (Kunststoff Handbuch Vol 7 (1983) ISBN 3-446-13614-2, p.428 ff).
The use of such TPU for biomedical applications is described, e.g., by Gogolewski in Colloid Polym. Sci 267 757-785 (1989). In particular, the chemistry, structure-property relations, tissue-material interaction, surface properties, biomedical use, and compatibility properties of biomedical polyurethanes are discussed. On page 782, Gogolewski concludes that: "Biocompatible and blood compatible polyurethane elastomers with unique physical and mechanical properties resulting from the hard-segment-soft-segment microphase segregation, are materials of choice for a number of biomedical applications".
Gogolewski further indicates that for biomedical applications, the two-step solution polymerization process which leads to polyurethanes having better physical characteristics, is preferred to one-step solution or melt polymerizations. The purity of reactants and polymerization media is critical to the final properties of polyurethanes. Factors affecting the purity of biomedical polyurethanes include the effective removal from the polymer of catalyst residues, low molecular weight fractions, processing aids, etc. The purity of the biomedical polyurethane determines to a great extent their in vivo performance (i.e. biocompatibility, blood compatibility, molecular stability).
Research on polyurethanes has continued since then, with the goal of developing the `ultimate` biomedical polyurethanes of tomorrow.
In recent years, many authors and companies have applied for patents for so-called biocompatible polyurethanes. For instance, G. Wick, Akzo GmbH, in German Auslegeschrift 3,643,465 (1986) describes a process for the production of biocompatible polyurethanes by the reaction of cycloaliphatic diisocyanates with a macrodiol to form a pre-adduct exhibiting NCO groups, wherein the diisocyanate to macrodiol molar ratio is from 3:1 to 33:1. Chain extension of the pre-adduct is effected with a mixture consisting of low-molecular-weight aliphatic diol and an aliphatic and/or cycloaliphatic macrodiol, wherein the aliphatic diol contains trimethylhexanediol within the mixture of the chain extenders. The addition of tin catalysts is prescribed in the embodiments given as examples.
In European Patent 0,461,375 and U.S. Pat. No. 5,133,742, a thermoplastic polyurethane (TPU) is described which is suitable for medical purposes. The preferred TPU described is synthesized from polycarbonate diol (molecular weight 1898), MDI, and 1,4-butanediol.
In PCT WO 92/04390, M. SZYCHER, Polymedica Industries Inc., describes other biostable polyurethanes. The polyurethanes described therein are synthesized from organic diisocyanates which are preferably the reaction product of aliphatic and/or cycloaliphatic diisocyanates with polycarbonate diol, and chain-extended with diol, diamine or a mixture of diamine and alkanolamine. Example 1 substantiates the use of tin catalysts.
E. Muller discovered as long ago as 1969 (see Angew. Makromol. Chemie 14 (1970), 75-86) that polyurethane elastomers having the highest resistance to hydrolysis are obtained from 1,6-hexanediol polycarbonate.
Gogolewski indicates that aliphatic polyurethanes are to be preferred to the aromatic polyurethanes for biomedical purposes.
However, aliphatic or cycloaliphatic polyisocyanates react with diol components too slowly. This resulted in the addition of catalysts to the reaction mixtures according to all known processes of the state of the art. Tin octoate, dibutyl tin dilaurate and/or tertiary amines, such as, for example, diazabicyclooctane (DABCO), have proved to be useful as catalysts.
Therefore, it is an object of the present invention to make available polyurethanes which are as free as possible from additives and which are produced without the addition of catalysts. The polyurethanes should be synthesized from aliphatic and/or cycloaliphatic diisocyanates, and as a result constitute pure polyurethanes which can also be used in medical technology.
All known processes of the state of the art which are employed to produce TPUs operate at temperatures which are as low as possible in order to avoid any unwanted side reactions. The most important side reactions to be avoided are the dimerization of diisocyanates, trimerization, formation of carbodiimide, formation of allophanate and formation of biuret.
In the synthesis of TPUs, one particular factor which must be taken into account is the formation of allophanate with the occurrence of molecular branching. Kunststoffhandbuch Vol. 7 Polyurethane (1983) at page 82, suggests that these reactions can also be carried out without catalysts at temperatures of around 120.degree. to 140.degree. C.
Synthesis of TPUs is customarily effected via NCO prepolymers. According to D. Dieterich in Houben-Weyl, Vol E 20, pp 1613-1617, it is the catalysts which influence the composition of the products. The temperature (i.e. below 100.degree. C.), the reaction time and the mode of addition play a less significant role in the composition.
From the publications disclosed hereinabove, it is evident that for the synthesis of TPUs via NCO prepolymers and semiprepolymers temperatures below 100.degree. C. are preferred.
For the production of transparent, non-yellowing elastomers, and in particular for biomedical applications, prepolymers based on 1,6-bis-[isocyanate]-hexane (i.e. HDI) or 5-isocyanate-3-(isocyanatemethyl)-1,3,3-trimethylcyclohexane (i.e. IPDI) can be used. For glycol extension of these prepolymers, a considerable amount of catalysis has to be effected (see, for example, D. Dieterich in Houben-Weyl, Vol E 20, p. 1637 and the bibliography therein). From the processes known from the literature, one of ordinary skill in the art would conclude that aliphatic TPUs cannot be produced without the use of catalysts.
For these reasons, it is surprising that in accordance with the present invention it is possible to produce particularly pure aliphatic TPUs of high mechanical quality by operating at temperatures above 100.degree. C. without the addition of catalysts.